Density functional computations of Rh(I)-catalysed hydroacylation of acetic aldehyde and ethene

Density functional theory has been used to study Rh(I)-catalysed hydroacylation of acetic aldehyde and ethene. All the intermediates and the transition states were optimised completely at the B3LYP/6-311+ + G(d,p) level (LANL2DZ(d) for Rh, P). Calculation results confirm that Rh(I)-catalysed hydroacylation of acetic aldehyde and ethene is endothermic, and the total absorbed energy is about 47 kJ/mol. The hydroacylation involves four possible reaction channels, going mainly through Rh–ethene–aldehyde complexes, Rh–ethene–carbonyl complexes, Rh-ethanyl-carbonyl complexes, and Rh-ketone complexes. The formation of Rh–ethene–carbonyl complexes (i.e. Rh(I)-catalysed oxidative addition of aldehyde) is the rate-determinating step for the Rh(I)-catalysed hydroacylation. And the energy barriers of the H-transfer reaction are lower than those of the C–C bond-forming reaction, and thus the H-transfer reaction is prior to the C–C bond-forming reaction. Therefore, the dominant reaction channels predicted theoretically are the reaction channels “a” and “b”, which is well in agreement with the experiments.     

Density functional studies on copper-catalysed asymmetric aziridination of diazoacetate with imines

Density functional theory has been used to study copper(I)-catalysed aziridination of diazoacetate with imines. All the intermediates and the transition states were optimised completely at B3LYP/6-31G(d) level. Calculation results confirm that copper(I)-catalysed aziridination of diazoacetate with imines is exothermic, and the total released Gibbs free energy is about ? 170 kJ/mol. Copper(I)-catalysed aziridination has two reaction modes: I and II, and thus the reaction mode I is dominant. The formation of the copper(I)–carbene–imine complex M3 (i.e. the attack of imines on copper–carbon(carbene) of copper–carbene intermediate M2) is the rate-determining step and the chirality-limiting step for copper-catalysed asymmetric aziridination. The reaction channel CA2 → M1a → TS1a → M2 → TS2a2 → M3a2 → TS3a2 → M4a2 → P1 is the most favourable one. The dominant products predicted theoretically are of (R)-chirality.     

Mechanism of intermolecular hydroacylation of vinylsilanes catalyzed by a rhodium(I) olefin complex: a DFT study

Density functional theory (DFT) was used to investigate the Rh(I)-catalyzed intermolecular hydroacylation of vinylsilane with benzaldehyde. All intermediates and transition states were optimized completely at the B3LYP/6-31G(d,p) level (LANL2DZ(f) for Rh). Calculations indicated that Rh(I)-catalyzed intermolecular hydroacylation is exergonic, and the total free energy released is −110 kJ mol⁻¹. Rh(I)-catalyzed intermolecular hydroacylation mainly involves the active catalyst CA2, rhodium–alkene–benzaldehyde complex M1, rhodium–alkene–hydrogen–acyl complex M2, rhodium–alkyl–acyl complex M3, rhodium–alkyl–carbonyl–phenyl complex M4, rhodium–acyl–phenyl complex M5, and rhodium–ketone complex M6. The reaction pathway CA2 + R2 → M1b → T1b → M2b → T2b1 → M3b1 → T4b → M4b → T5b → M5b → T6b → M6b → P2 is the most favorable among all reaction channels of Rh(I)-catalyzed intermolecular hydroacylation. The reductive elimination reaction is the rate-determining step for this pathway, and the dominant product predicted theoretically is the linear ketone, which is consistent with Brookhart’s experiments. Solvation has a significant effect, and it greatly decreases the free energies of all species. The use of the ligand Cp′ (Cp′ = C₅Me₄CF₃) decreased the free energies in general, and in this case the rate-determining step was again the reductive elimination reaction.     

Enhanced production of ginsenoside Rh2(S) from PPD-type major ginsenosides using BglSk cloned from Saccharibacillus kuerlensis together with two glycosidase in series

BackgroundGinsenoside Rh2(S) is a promising compound for the prevention of various kinds of cancers, inflammation, and diabetes. However, due to its low concentration (<0.02%), researchers are still trying to find an efficient glycoside hydrolase for the scaled-up production of Rh2(S).MethodThree glycoside hydrolases (BglBX10, Abf22-3, and BglSk) were cloned in Escherichia coli BL21 (DE3) and the expressed recombinant enzyme was used for the scaled-up production of Rh2(S) through the conversion of PPD-type (protopanaxadiol) major ginsenosides (Rb1, Rc, and Rd, except Rb2) extracted from Korean red ginseng. Specific and specialized bioconversion pathways were designed that evolved the initial bioconversion of PPD-mix → Rg3(S) → Rh2(S). The reaction was started with 50 mg/mL of PPD-mix, 20 mg/mL of BglBX10, Abf22-3, and BglSk in series, respectively. The process was completed in a 10 L jar fermenter with a 5 L working volume at 37 °C for 48 hrs.ResultsThe designed bioconversion pathways show that Abf22-3 and BglBX10 were responsible for the conversion of Rb1, Rc and Rd → Rg3(S), and then Rg3(S) was completely transformed to Rh2(S) by BglSk. As a result, 15.1 g of ginsenoside Rh2(S) with 98.0 ± 0.2% purity was obtained after strict purification using the Prep-HPLC system with a 100 φ diameter column. Additionally, BglSk was also investigated for its production activity with seven different kinds of PPD-mix type ginsenosides.ConclusionOur pilot data demonstrate that BglSk is a suitable enzyme for the gram unit production of ginsenoside Rh2(S) at the industrial level.     

Screening of bromotyramine analogues as antifouling compounds against marine bacteria

Rapid and efficient synthesis of 23 analogues inspired by bromotyramine derivatives, marine natural products, by means of CuSO₄-catalysed [3+2] alkyne–azide cycloaddition is described. The final target was then assayed for anti-biofilm activity against three Gram-negative marine bacteria, Pseudoalteromonas ulvae (TC14), Pseudoalteromonas lipolytica (TC8) and Paracoccus sp. (4M6). Most of the synthesised bromotyramine/triazole derivatives are more active than the parent natural products Moloka’iamine (A) and 3,5-dibromo-4-methoxy-β-phenethylamine (B) against biofilm formation by the three bacterial strains. Some of these compounds were shown to act as non-toxic inhibitors of biofilm development with EC₅₀ < 200 μM without any effect on bacterial growth even at high concentrations (200 μM).     

The structure of 2-carboxyquinolinatobis(triphenylphosphite)rhodium(I)

2-Carboxyquinolinatobis(triphenylphosphite)rhodium (I) was prepared by means of the following reaction: [Rh(Qin)(CO)₂] + 2P(OPh)₃→ [Rh(Qin)(P(OPh)₃)₂] + 2CO It crystallizes in the triclinic space groupP] witha = 12.406,b = 18.702,c = 9.547 Å, α = 76.36, β = 111.35, γ = 97.88^o and Z = 2. The structure was determined from 4520 observed reflections. the final R value was 0.051. The RhP bond distances may indicate (although the difference is only about 3σ) that the nitrogen atom the chelate ring has the largest trans influence. The chelate ring is significantly folded along the N---O axis.     

DFT studies of hydrocarbon combustion on metal surfaces

Catalytic combustion of hydrocarbons is an important technology to produce energy. Compared to conventional flame combustion, the catalyst enables this process to operate at lower temperatures; hence, reducing the energy required for efficient combustion. The reaction and activation energies of direct combustion of hydrocarbons (CH?→?C?+?H) on a series of metal surfaces were investigated using density functional theory (DFT). The data obtained for the Ag, Au, Al, Cu, Rh, Pt, and Pd surfaces were used to investigate the validity of the Brønsted-Evans-Polanyi (BEP) and transition state scaling (TSS) relations for this reaction on these surfaces. These relations were found to be valid (R²?=?0.94 for the BEP correlation and R²?=?1.0 for the TSS correlation) and were therefore used to estimate the energetics of the combustion reaction on Ni, Co, and Fe surfaces. It was found that the estimated transition state and activation energies (E_TS?=??69.70 eV and E_a?=?1.20 eV for Ni, E_TS?=??87.93 eV and E_a?=?1.08 eV for Co and E_TS?=??92.45 eV and E_a?=?0.83 eV for Fe) are in agreement with those obtained by DFT calculations (E_TS?=??69.98 eV and E_a?=?1.23 eV for Ni, E_TS?=??87.88 eV and E_a?=?1.08 eV for Co and E_TS?=??92.57 eV and E_a?=?0.79 eV for Fe). Therefore, these relations can be used to predict energetics of this reaction on these surfaces without doing the time consuming transition state calculations. Also, the calculations show that the activation barrier for CH dissociation decreases in the order Ag ? Au ? Al ? Cu ? Pt ? Pd ? Ni?>?Co?>?Rh?>?Fe.     

Nickel/zinc-catalyzed decarbonylative addition of anhydrides to alkynes: A DFT study

Density functional theory (DFT) was used to investigate the nickel- or nickel(0)/zinc- catalyzed decarbonylative addition of phthalic anhydrides to alkynes. All intermediates and transition states were optimized completely at the B3LYP/6-31+G(d,p) level. Calculated results indicated that the decarbonylative addition of phthalic anhydrides to alkynes was exergonic, and the total free energy released was ?87.6 kJ mol^?1. In the five-coordinated complexes M4a and M4b, the insertion reaction of alkynes into the Ni-C bond occurred prior to that into the Ni-O bond. The nickel(0)/zinc-catalyzed decarbonylative addition was much more dominant than the nickel-catalyzed one in whole catalytic decarbonylative addition. The reaction channel CA→M1'→T1'→M2'→T2'→M3a'→M4a'→T3a1'→M5a1' →T4a1'→M6a'→P was the most favorable among all reaction pathways of the nickel- or nickel(0)/zinc- catalyzed decarbonylative addition of phthalic anhydrides to alkynes. And the alkyne insertion reaction was the rate-determining step for this channel. The additive ZnCl₂ had a significant effect, and it might change greatly the electron and geometry structures of those intermediates and transition states. On the whole, the solvent effect decreased the free energy barriers.

Oligonucleotides Incorporating 7-(Aminoalkyn-1-yl)-7-deaza-2′-deoxyguanosines: Duplex Stability and Phosphodiester Hydrolysis by Exonucleases

Abstract

Self-complementary {[5′-d(G-C)₄]₂} and non-selfcomplementary oligonucleotides [5′-d(TAG GTC AAT ACT) ? 3′-d(ATC CAG TTA TGA)] containing 7-(ω-aminoalkyn-1-yl)-7-deaza-2′-deoxyguanosines (1a–c) (1) and 7-deaza-2′-deoxyguanosine instead of dG were studied regarding their thermal stability as well as their phosphodiester hydrolysis by either 3′ → 5′- or 5′ → 3′ – phosphodi esterase studied by MALDI-TOF MS.     

Relationships Between Single Nucleotide Polymorphisms of the H-FABP Gene and Slaughter and Meat Quality Traits in Chicken

Using PCR-SSCP with five primer pairs, we detected six single nucleotide polymorphisms of the H-FABP gene: 332G → A, 534G → A, 783C → T, 835C → T, 1198T → C, and 2329C → T. Chi-square results showed significant differences (P < 0.05) in genotype frequency among breeds in Fragment 1 and extremely significant differences (P < 0.01) in Fragments 2–4. We found a significant association between Fragment 2 genotype and muscle fiber number, Arg and Thr (P < 0.05); between Fragment 3 genotype and living weight, carcass weight, breast muscle weight, abdominal fat weight, and abdominal fat percentage (P < 0.05); between Fragment 4 genotype and Thr, Phe, and inosinic acid (P < 0.05). It was concluded that H-FABP was the major gene influencing slaughter performance and meat quality or was linked with the major gene in these strains and that the C783T mutation could be used as a candidate molecular genetic marker for breeding selection. The combination M1C2–B2B2–D1D1 is an ideal model for breeding in these strains because it can improve slaughter and meat quality traits.     

Biosynthesis of the carbohydrate moieties of arabinogalactan proteins by membrane-bound β-glucuronosyltransferases from radish primary roots

A membrane fraction from etiolated 6-day-old primary radish roots (Raphanus sativus L. var hortensis) contained β-glucuronosyltransferases (GlcATs) involved in the synthesis of the carbohydrate moieties of arabinogalactan proteins (AGPs). The GlcATs transferred [¹⁴C]GlcA from UDP-[¹⁴C]GlcA on to β-(1 → 3)-galactan as an exogenous acceptor substrate, giving a specific activity of 50–150 pmol min^?1 (mg protein)^?1. The enzyme specimen also catalyzed the transfer of [¹⁴C]GlcA on to an enzymatically modified AGP from mature radish root. Analysis of the transfer products revealed that the transfer of [¹⁴C]GlcA occurred preferentially on to consecutive (1 → 3)-linked β-Gal chains as well as single branched β-(1 → 6)-Gal residues through β-(1 → 6) linkages, producing branched acidic side chains. The enzymes also transferred [¹⁴C]GlcA residues on to several oligosaccharides, such as β-(1 → 6)- and β-(1 → 3)-galactotrioses. A trisaccharide, α-l-Araf-(1 → 3)-β-Gal-(1 → 6)-Gal, was a good acceptor, yielding a branched tetrasaccharide, α-l-Araf-(1 → 3)[β-GlcA-(1 → 6)]-β-Gal-(1 → 6)-Gal. We report the first in vitro assay system for β-GlcATs involved in the AG synthesis as a step toward full characterization and cloning.     

Association between clinical expression and molecular heterogeneity in β-thalassemia Tunisian patients

Beta-thalassemia is the most frequent hereditary blood disorder in Tunisia because of its geographic localization and history. This pathology is characterized by a complex multisystem process with genetic and biochemical interactions. The aim of this work was to establish phenotype/genotype association through studying the distribution and the relationship between β-thalassemia and α-thalassemia mutations and three polymorphic markers: the C → T polymorphism at ?158 of the Gγ gene, the RFLP haplotype and the repeated sequence (AT)_xT_y in the β globin silencer, in two groups of β-thalassemia major and β-thalassemia intermedia (TI) patients. Statistical analysis has shown that moderate expression seen in TI patients was significantly associated to β⁺ ?87 (C → G), ?30 (T → A) and IVSI-6 (T → C) mutations, haplotypes VIII, IX and Nb and to XmnI polymorphism. The regression analysis of combined genotypes (mutation/XmnI/RFLP haplotype) revealed that they contribute to justify 17.1 % of clinical expression diversity (p < 0.05). Among the studied genotypes the XmnI polymorphism seems to be the most determinant modulating factor, followed by the β-thalassemia mutation and RFLP haplotype. Our findings highlight the heterogeneity of molecular background of β-thalassemia that would be responsible of clinical variability.     

Association of angiotensin-converting enzyme and endothelial Nitric Oxide synthase gene polymorphisms with vascular disease in ESRD patients in a Chinese population

Background The effect of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and endothelial Nitric Oxide synthase (eNOS) gene G894 → T on vascular disease in end-stage renal disease (ESRD) patients was rarely studied previously. We investigated such effect in a Chinese population. Methods A total of 153 ESRD patients with vascular disease (88 men and 65 women; mean age ± SD: 54.0 ± 13.2) were recruited. Polymerase chain reaction was used to classify the ACE genotypes as II, ID and DD and the eNOS genotypes as GG, GT, and TT. Analyses were performed in ESRD patients with vascular disease (n = 153) and the age-matched controls (n = 148). Results The frequencies of ACE DD and eNOS TT genotypes and ACE D and eNOS T alleles in ESRD patients with vascular disease were significantly higher than those in the controls (P < 0.05). There was a significant interaction between ACE I/D alleles and eNOS G894 → T polymorphism: adjusted odds ratio 2.128 (95%CI 1.022–4.434, P = 0.017). Conclusions These results indicated that the etiology of vascular disease in ESRD patients is associated with ACE and eNOS (G894 → T) gene polymorphisms. Our data also suggest that an interaction effect may exist between ACE (I/D) and eNOS (G894 → T) polymorphism in increasing the risk of vascular complications in ESRD patients     

Impacts of terminal (4R)-fluoroproline and (4S)-fluoroproline residues on polyproline conformation

Many interests have been focused on prolyl cis–trans isomerization which is related to protein folding and isomer-specific biochemical recognition. Since polyproline can adopt either type I (PPI) helices with all cis amide bonds or type II (PPII) helices with all trans amide bonds, it has been a valuable model to study the prolyl isomerization. Recent studies have shown that stereoelectronic effects govern the stability of PPII structure and the rate of PPII → PPI conversion. To further explore the terminal stereoelectronic effects on polyproline conformation, herein we synthesized a series of host–guest peptides in which (2S,4S)-4-fluoroproline (flp) or (2S,4R)-4-fluoroproline (Flp) residues are incorporated into the C- or N-terminal end of a peptide and studied the thermodynamic and kinetic consequences on polyproline conformation. Circular dichroism measurements revealed that inserting 4-fluoroproline residues into the C terminus of a polyproline peptide induces a great stereoelectronic effect on PPII stability and PPII → PPI conversion rates. From the C terminus, a (Flp)₃ triplet stabilizes PPII structure and increases the transition barrier of PPII → PPI conversion by 1.53 kJ mol^?1 while a (flp)₃ triplet destabilizes PPII conformation and reduce the PPII → PPI transition barrier by 4.61 kJ mol^?1. In contrast, the 4-fluoroproline substitutions at the N terminus do not exhibit distinct stereoelectronic effects on PPII stability and PPII → PPI conversion rates. Our data demonstrate that the C-terminal stereoelectronic effects have a more dramatic impact on PPII stability and PPII → PPI conversion kinetics.     

Syntheses of all eight stereoisomers of conidendrin

ABSTRACT

All eight stereoisomers of conidendrin were synthesized from (1 R,2 S,3 S)-1-(4-benzyloxy-3-methoxyphenyl)-3-(4-benzyloxy-3-methoxybenzyl)-2- hydroxymethyl-1,4-butanediol ((+)-4) and its enantiomer with high optical purity. The configurations at 4-positions of the conidendrin stereoisomers were constructed by intramolecular Friedel-Crafts reaction of protected 4. After conversion to tetrahydronaphthalene intermediate 7a, the 2- and 3-position of tetrahydronaphthalene structure 7a were converted to 3a- and 9a-position of (+)-α-conidendrin (3a), respectively. By the epimerization process of 2- or 3-position of 7a, the other diastereomers were obtained. All enantiomers were also synthesized from (?)-4.     

Improved peroxyl radical scavenging TOSC assay to quantify antioxidant capacity using SIFT-MS

Abstract

We report a new, fast, sensitive variation of the total oxyradical scavenging capacity (TOSC) assay for measuring the antioxidant capacity of pure compounds, plant extracts and biological fluids using selected ion flow tube mass spectrometry (SIFT-MS). The TOSC assay examines the partial inhibition of ethene formation in the presence of antioxidants that compete with α-keto-γ-methiolbutyric acid (KMBA) for reactive oxygen species. The SIFT-MS-TOSC assay takes 15 s for each ethene analysis and the time interval between consecutive analyses is 20 s. We demonstrate the method by monitoring the antioxidant capacity of several standard radical scavengers of peroxyl radicals. For peroxyl radicals the measured SIFT-MS-TOSC concentrations necessary to produce 50% inhibition of radical reaction with KMBA are 6.1 ± 0.3 μM for Trolox, 5.7 ± 0.3 μM for ascorbic acid, 8.4 ± 0.4 μM for uric acid and 38 ± 2 μM for reduced glutathione.     

The synthesis of (Z)-4-oxo-4-(arylamino)but-2-enoic acids derivatives and determination of their inhibition properties against human carbonic anhydrase I and II isoenzymes

The synthesis of (Z)-4-oxo-4-(arylamino)but-2-enoic acid (4) derivatives containing structural characteristics that can be used for the synthesis of several active molecules, is presented. Some of the butenoic acid derivatives (4a, 4c, 4e, 4i, 4j, 4k) are synthesized following literature procedures and at the end of the reaction. In addition, structures of all synthesized derivatives (4a–4m) were determined by ¹H-NMR, ¹³C-NMR and IR spectroscopy. Carbonic anhydrase is a metalloenzyme involved in many crucial physiologic processes as it catalyzes a simple but fundamental reaction, the reversible hydration of carbon dioxide to bicarbonate and protons. Significant results were obtained by evaluating the enzyme inhibitory activities of these derivatives against human carbonic anhydrase hCA I and II isoenzymes (hCA I and II). Butenoic acid derivatives (4a–4m) strongly inhibited hCA I and II with K_is in the low nanomolar range of 1.85?±?0.58 to 5.04?±?1.46?nM against hCA I and in the range of 2.01?±?0.52 to 2.94?±?1.31?nM against hCA II.     

N-(4-Hydroxyphenyl)-3,4,5-trimethoxybenzamide derivatives as potential memory enhancers: synthesis,biological evaluation and molecular simulation studies

The present paper describes the synthesis, biological evaluation and molecular simulation studies of a series of N-(4-hydroxyphenyl)-3,4,5-trimethoxybenzamide derivatives with N,N-dialkylaminoethoxy/propoxy moiety as potential memory enhancers with acetylcholinesterase-inhibiting activity having IC₅₀ in low micromolar range (4.0–16.5 μM). All the compounds showed a good degree of agreement between in vivo and in vitro results as most of these derivatives showed dose-dependent increase in percent retention. Compound 10a showed significant % retention of 84.73 ± 4.51 as compared to piracetam (46.88 ± 5.42) at 3 mg kg^?1 and also exhibited a maximal percent inhibition of 97% at 50 μM. Molecular docking, MM-GBSA and molecular simulation studies were performed establishing a correlation between the experimental biology and in silico results. In silico results indicate that all the compounds have better docking scores and predicted binding free energies as compared to cocrystallized ligand with the best potent ligand retaining conserved hydrophobic interactions with residues of catalytic triad (HIS447), catalytic anionic site (CAS) (TRP86, TYR337, PHE338) and peripheral anionic site (PAS) (TYR72, TYR124, TRP286 and TYR341). Root mean square deviation (RMSD = 2.4 Å) and root mean square fluctuations of 10a–AChE complex during simulation proved its stable nature in binding toward acetylcholinesterase. The docked conformation of 10a and other analogs at the binding site have also been simulated with polar and nonpolar interactions interlining the gorge residues from PAS to catalytic triad.